Genscan for <Emphasis Type="Italic">Arabidopsis</Emphasis> is a valuable tool for predicting sponge coding sequences

Although the first sponge genome project has already started releasing completed sequences, only a very small number of annotated sponge genomic sequences has so far been published. In addition, no gene-prediction software optimised for sponges is available yet. In the present paper, we present the performance of Arabidopsis-optimised Genscan as tested on sponge genes. All genes whose genomic and complete CDS sequences are deposited in the NCBI nucleotide database were retrieved and used as the test set. The 18 test genes are composed of 114 coding exons. The sensitivity and specificity, respectively, of all exons were predicted with 83.3% and 79.2%, internal exons with 88.5% and 80.2%, donor with 93.8% and 85.7%, acceptor with 89.6% and 78.9%, initiation with 94.4% and 85%, and termination sites with 72.2% and 81.3%. The results are compared with prediction results obtained with Genscan for vertebrates and GeneMark.hmm ES-3.0 for Arabidopsis. The surprising finding is that although the animals are the source of sequences, the best results (more than 80% accuracy in predicting complete exons) were obtained by Genscan optimised for a plant A. thaliana. Although the sample is small, the results lead to the conclusion that Genscan for Arabidopsis is a valuable tool for predicting coding sequences in sponges and could be of great help in annotating sponge genes. Dedicated to Prof. Dr.Sc. Vera Gamulin, a remarkable lady who passed away too soon and suddenly.     

Tumour‐derived exosomes: Tiny envelopes for big stories

The discovery of exosomes, which are small, 30–100 nm sized extracellular vesicles that are released by virtual all cells, has initiated a rapidly expanding and vibrant research field. Current investigations are mainly directed toward the role of exosomes in intercellular communication and their potential value as biomarkers for a broad set of diseases. By horizontal transfer of molecular information such as micro RNAs, messenger RNAs or proteins, as well as by receptor–cell interactions, exosomes are capable to mediate the reprogramming of surrounding cells. Herein, we review how especially cancer cells take advantage of this mechanism to influence their microenvironment in favour of immune escape, therapy resistance, tumour growth and metastasis. Moreover, we provide a comprehensive microarray analysis (n > 1970) to study the expression patterns of genes known to be intimately involved in exosome biogenesis across 26 different cancer entities and a normal tissue atlas. Consistent with the elevated production of exosomes observed in cancer patient plasma, we found a significant overexpression especially of RAB27A, CHMP4C and SYTL4 in the corresponding cancer entities as compared to matched normal tissues. Finally, we discuss the immune‐modulatory and anti‐tumorigenic functions of exosomes as well as innovative approaches to specifically target the exosomal circuits in experimental cancer therapy.     

Genes for mevalonate biosynthesis in<Emphasis Type="Italic"> Phycomyces</Emphasis>

Terpenoids or isoprenoids constitute a vast family of organic compounds that includes sterols and carotenoids. The terpenoids in many organisms share early steps in their biosynthesis, including the synthesis of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) and its conversion to mevalonate. We have cloned and characterised the genes hmgS for HMG-CoA synthase and hmgR for HMG-CoA reductase from the Zygomycete Phycomyces blakesleeanus. Single copies of these genes are present in the Phycomyces genome. The predicted product of hmgS is largely hydrophilic and that of hmgR has eight putative transmembrane segments and a large hydrophilic domain. The hydrophilic domain suffices for catalytic activity, as shown by expressing it in Escherichia coli. Several features in the promoter of hmgS and in HMG-CoA reductase resemble motifs known to be involved in sterol-mediated regulation and sterol sensing. Carotene-overproducing mutants contain more hmgS mRNA than the wild type, possibly in response to an increased demand for HMG-CoA.